8alpha-(4-phenyl-1-piperazyl)-4alpha, 5, 6, 7, 8alpha-hexahydro-4h-1-benzopyrans and process



United States Patent 8a (4-PHENYL 1 PIPERAZYL)-4a,5,6,7,8a-HEXA- HYDRO-4H-l-BENZOPYRANS AND PRGCESS Robert Norman Schut, Edwardsburg, Mich., assignor to Miles Laboratories, Inc., Elkhart, Ind., a corporation of Indiana No Drawing. Original application July 16, 1964, Ser. No. 383,239, now Patent No. 3,309,370, dated Mar. 14, 1967. Divided and this application Sept. 2, 1966, Ser. No. 596,358

8 Claims. '(Cl. 260-268) ABSTRACT OF THE DISCLOSURE The reaction of phenyl piperazine enamines with 41,8- unsaturated aldehydes and aromatic ketones leads to novel aminopyran derivatives which upon heating undergo a rearrangement to form bicyclo alkanone derivatives useful as anti-inflammatory and analgetic agents.

This application is a divisional application of the copending application of Robert Norman Schut, Serial No. 383,239, filed July 16, 1964, now US. Patent 3,309,370 for Product.

This invention relates to bicycloalkanones. In one of its more particular aspects this invention relates to bicycloalkanone derivativess having pharmacological activity.

The compounds of this invention constitute a series of piperazyl substituted bicycloalkanones which can be represented by means of the structural formula:

in which R is a hydrogen atom or an aryl radical. R is a hydrogen atom or an alkyl radical. R is a hydrogen atom, a halogen atom, or a haloalkyl radical and X is a polycarbon lower alkylene radical.

The above structural formula shows the compounds of this invention in the form of their free bases. However, these compounds can be provided in the form of any of a number of salts. For example, the compounds can be prepared in the form of their hydrochlorides, hydrobromides, maleates, oxalates and other pharmacologically acceptable salts. In general the free bases can be reacted with any acid, inorganic or organic, which will enter into salt formation with these bases.

The compounds of this invention can be prepared by reacting the appropriate phenyl substituted piperazine enamine of a cycloalkanone with an a ti-unsaturated alderyde in a suitable solvent such as benzene. No catalyst is ordinarily required. The enamine can be readily prepared by reacting the appropriate cyclo-alkanone with the desired phenyl substituted piperazine preferably in a suitable solvent such as toluene and in the presence of an acid catalyst such as p-toluenesulfonic acid. The reaction is usually conducted at reflux in order to liberate water. The reactions involved in the preparation of the novel bicycloalkanones of this invention can be illustrated by means of the following reaction sequence in which the various substituents are as above defined.

The reaction of phenyl substituted piper azine enamines with a,,8-unsaturated aldehydes and aromatic ketones leads to novel aminopyran derivatives of the general formula:

wherein R R R and X are as above defined and R is a hydrogen atom or an aryl radical. I

Where R is a hydrogen atom, that is, where the unsaturated carbonyl compound is an a,,8-unsaturated aldehyde, heating the aminopy-ran derivative in a mixture of triethylamine and dimethylformamide results in rearrangement to the corresponding bicycloalkanone as shown in the following reaction sequence:

Where R is an aryl radical, for example phenyl, the aminopyran derivative undergoes a retrocondensation in the presence of a polar solvent to produce an alkylated enamine derivative but does not undergo an internal Mannich reaction to produce the bicycloalkanone. Thus, in the case where R is aryl the aminopyran derivative reacts as follows: 1

EXAMPLE I 2- (i-PHENYL-l-PIPERAZYL) 9OXOBICYCLO [3.3.11'NONANE A. 1- (4-phenyl-1-piperazyl) cyclohexene A solution of 162 g. (1.0 mole) of l-phenylpiperazine, 98 g. (1.0 mole) of cyclohexanone and 1 g. of p-toluene sulfonic acid in 300 ml. of toluene was heated under reflux for 1 day. The water liberated was collected in a Dean-Stark trap. The solvent was distilled and the residue was distilled in vacuo, B.P. 125 140 (0.2 mm.) and recrystallized from 2-propanol, M.P. 112114, yield 84%.

Analysis.Calcd. for C H N N (basic), 5.79. Found: N (basic), 5.92.

B. 8a-(4-phenyl-I-piperazyl)-4a,5,6,7,8,8a-hexahydro- 4H-1-benzopyran To a stirred solution of 14.1 g. 0.0583 mole) of 1-(4- phenyl-l-piperazyl)cyclohexene in 50 ml. of dry benzene was added a solution of 4.5 g. (0.080 mole) of acrolein (dried over MgSO in 25 ml. of dry benzene over a 30 P5 59 1660 o-o=o 1235, 1150 and 1070 cm.- (ether) The n.m.r. spectrum (CDCl showed resonance peaks due to the 2 and 3 protons at 3.87 T (doublet) and 5.41 T (multiplet) respectively.

Analysis.Calcd. for C H N O: C, 76.51; H, 8.72; N (total), 9.40; N (basic), 4.70. Found: C, 76.34; H, 8.66; N (total), 9.49; N (basic), 4.69.

The benzene-ether filtrate from above was concentrated in vacuo to give a white solid. This material was broken up, stirred with Skelly A (n-pentane), collected and recrystallized from benzene-Skelly B (n-hexane) to give 7.6 g. of white crystals, M.P. 113114, undepressed when mixed with an analytical sample of the aminopyran. The total yield was 12.2 g. (71% C. 2 (4 phenyl-1 -piperazyl -.-0x0bicycl0 [3 .3 .1 nonane To a solution of 9.03 g. of the aminopyran in ml. of freshly distilled dimethylformamide was added 3.1 g. of triethylamine. The solution was heated in a nitrogen atmosphere for 12 hours at 70-75 The solvents were removed by distillation in vacuo and the residue was stirred with Skelly B. The crude solid weighed 7.61 g., M.P. 100-105;

.ggg 1715 our- Recrystallization from Skelly B and a few drops 0i benzene followed by recrystallization from a small quantity of methanol produced the analytical sample, M.P. 129- 131.

Analysis.-Calcd. for C H N O: C, 76.51; H, 8.72; N, 9.40. Found: C, 76.26; H, 8.45; N, 9.61.

D. 2- (4-ph*enyl-1 -pi perazyl -9-0x0bicycl0 [3 .3 .1 nonane hydrocloride A 10.0 g. sample of the free base was suspended in 2-propanol and treated with a slight excess of 1 moleequivalent of 3.4 N HCl-i-Pr-OH. The mixture was heated and the salt dissolved by addition of the minimal amount of water. Analytically pure monohydrochloride was isolated (6.0 g.), M.P. 184-185.

AnaZysis.Calcd. for C H N O'HCI: Cl, 10.59; N, 8.38. Found: Cl, 10.47; N, 8.26.

EXAMPLE II 2 (4-PHllNYL-1-PIPERAZYL) -3-METHYL-0-OXOBICYCLO [3.3.1]NONANE A. 8a- (4-phenyl-1-piperazyl) -3-methyl-4a,5,6,7,8,8ahexahydr0-4H-1 benzopyran To a solution of 48.4 g. (0.20 mole) of 1-(4-phenyl- 1-piperazy1)cyclohexene dissolved in a minimal amount of dry benzene was added a solution of 17.5 g. (0.25 mole) 'of methacrolein in 25 ml. of benzene. After being stored in the refrigerator for 5 days, the crystalline prod- CHCla "max.

1680 (m.), 1210, 1165, and 1130 (s.) cm."

Analysis.Calcd. for C H N O: C, 76.92; H, 8.97; N, 8.97. Found: C, 76.47; H, 8.84; N, 9.08.

B. 2- (4 -pheny l-1 -piperazyl -3 -methyl-9-0x0bicycl0 [3.3.1]nnane 1) Isolation from bicyclic aminoketone-aminopyran mixture.l n a typical 0.36 mole run, there was obtained 32.2 g. of aminopyran. The filtrate on dilution with Skelly A produced 25.0 g. of crude solid (bicyclic aminoketone). This material was dissolved in dilute hydrochloric acid and shaken with ether in order to remove neutral material. The aqueous layer was basified and extracted with chloroform. The dried extract was concentrated in vacuo and the residue was purified by warming in methanol, yield 6.38 g., M.P. 144-145. The analytical sample was prepared by recrystallization from Skelly A- benzene, M.P. 145 146 vggq 1705 cm.

Analysis.--Calcd. for C H N O: C, 76.92; H, 8.97; N, 8.97. Found: C, 76.37; H, 8.82; N, 9.28.

(2) lsom erization of aminopyran (A) to bicyclic aiminoketone (B).A solution of 14.0 g. of the aminopyran in 200 ml. of purified dimethylformamide and 25 ml. of triethylamine was heated under a nitrogen atmosphere at 85-90 for 2 days. The solvents were concentrated in vacuo and the residue dissolved in dilute hydrochloric acid. The free base was isolated as described above for the aminopyran, yield 1.2 g. (9%), M.P. 144146.

C. 2- (4-phenyl-1-piperazyl) -3-methyl-9-0xobicyclo [3.3 .1 nonane hydrobromide A 9.30 g. sample of the free base was dissolved in 125 m1. of ethyl acetate and treated with 9.58 ml. of 3.11 N- H-Br-i-PrOH. The precipitated salt was collected, washed with ethyl acetate and dried, yield 8.4 g. Recrystallization from i-PrOH-HgO gave 4.70 g. of product, M.P. 179- 180 (dec.),

v53 1715 cm."

Analysis.Calcd. for C20H28N2O"HBII Br. 20.33; N. 7.12. Found: Br. 20.72; N, 7.23.

EXAMPLE III 2-(4-PHENYL-1-PIPERAZYL) -7-CYCLOHEXYL-9- OXOBICYCLO[3.3.1]NONANE A. 1-(4-phenyl-1-piperazyl) -4-cyclohexylcyclohexene This enamine was prepared according to the procedure of Example IA using 4-cyclohexylcyclohexanone as the cycloalkanone. The product was isolated in yield of 80%, M.P. 177-179'.

Analysis.Calcd. for C H N N, 8.67. Found: N, 8.73.

B. 8a-(4-phenyl-1-piperazyl)-6-cycl0hexyl-4u,5,6,7,8, 8a-hexahydr0-4H 1 -benz0pyran To a stirred suspension of 64.8 g. (0.20 mole) of 1- (4 phenyl-l-piperazyl)-4-cyclohexylcyclohexene in 150 ml. of dry benzene and 150 ml. of dimethylformamide at 10 was added a solution of 13 g. of acrolein in 50 ml. of benzene. The mixture was swirled on the steam bath until all the solid material had dissolved. The solution was stirred for 30 minutes, allowed to stand at room temperature for 3 hours, then stored in the refrigerator overnight. The solid which had precipitated was collected and washed with Skelly A, yield 36.5 g., M.P. 108-1l0 (cloudy melt). Concentration .of the filtrate and stirring with Skelly A produced an additional 17.2 g. of product, M.P. 102-106, total yield 53.7 g. (71%). The analytical sample was prepared by recrystallization from benzene-Skelly B, M.P. 107109;

r355 1660 (111.) cm.'

Analysis.Calcd. for C H N O: N, 7.37; C, 78.95; H, 9.47; N, 7.37. Found: C, 78.58; H, 9.36; N, 7.47.

C. 2- (4-phenyl-1 -piperazyl) -7-cyclohexyl-9-0x0bicyclo- [3.3 .1 nonane A solution of 53.7 g. (0.14 mole) of aminopyran in 600 ml. of di-methylformamide and 60 ml. of triethylamine was heated at 75 -80 for 40 hours under a nitrogen atmosphere. Concentration in vacuo gave an orangecolored sirup. Stirring in Skelly A gave a greasy solid which was dissolved in benzene. Addition of excess dilute hydrochloric acid resulted in the formation of a crude hydrochloride. The acid filtrate was made basic and extracted with chloroform. Drying and concentration in vacuo gave an oil from which it was possible to obtain 2.0 g. of solid material by chilling in methanol; M.P. 135138;

.ggg 1710 cm.

- The crude hydrochloride mentioned above was also converted to the free base, yield 13.3 g., M.P. 124-125;

.539 1710 car- D. 2- (4-phenyl-I-piperazyl) -7-cycl0h exyl-9-ox0bicyclo- [3.3.1 -n0nane hydrochloride A 5.61 g. sample of the free base dissolved in warm 2-propanol-ether was treated with 5.22 ml. of 2.84 N- HCl-i-PrOH. On cooling a crystalline white salt formed, yield 4.6 g. Recrystallization from isopropyl alcohol gave 2.50 g. of purified product, M.P. -176 (dec.);

Analysis.Calcd. for C H N O-HCl: Cl, 8.51; N, 6.71. Found: Cl, 8.44; N, 6.71.

EXAMPLE IV A. 1-(4-phenyl-1-piperazyl) cyclopentene This enamine was prepared according to the procedure of Example IA using cyclopentanone as the cycloalkanone. The product was isolated in a yield of 61%, M.P. 101

Analysis.Calcd. for C H N N, 12.27. Found: N, 12.40.

7 B. 2- (4-phenyl-1-piperazyl) -8-oxobicyclo[3.2.l 1 octane Acrolein (ca. 0.25 mole) was added to a stirred solution of =1-(4-phenyl-1-piperazyl)cyclopentene in dry benzene. The temperature was maintained below 20 by means of an ice-bath. After standing in the refrigerator overnight, the solvent was distilled in vacuo. The light sirup was stirred in Skelly A to gradually give a greasy solid. Stirring this material with warm ether produced a light tan solid, yield 20.7 g. (37%), M.P. 128-13l;

V3 39 1740 cm.-

For further purification, the product was dissolved in dilute hydrochloric acid and the solution shaken with ether to remove neutral material. Regeneration of the free base and recrystallization from methanol give the bicyclic aminoketone as fine needles, M.P. 137 "-138".

Analysis.Calcd. for C H N O: C, 76.06; H, 8.45; N, 9.86. Found: C, 75.88; H, 8.78; N, 10.07.

C. 2-(4-phenyl-1-piperazyl) -8-oxobicyclo[3.2.1 ]octane hydrochloride hydrate A 23.6 g. sample (0.0831 mole) of the free base in 100 ml. of isopropyl alcohol and 250 ml. of warm ethyl acetate was treated with 29.3 ml. of 2.84 N HCl-i-PrOH (1 moleequiv.). The precipitated salt was recrystallized from aqueous isopropyl alcohol, yield 14.5 g., M.P. 196197 (dec.) with droplets of moisture appearing in the top portion of the tube during the measurement. The analysis indicated a hydrate and the infrared spectrum (KCl) showed only a very weak band in the 1750 cm.- region in agreement with carbonyl hydration.

Analysis. Calcd. for C H N O-HCl-H O: C], 10.47; N, 8.26. Found: Cl, 10.42; N, 8.45.

D. 2- (4-phenyl-1 -piperazyl) -8-ox0bicycl0 [3.2 .1] octane hydrochloride A sample of of the hydrate was heated for 10 hours in the Abderhalden pistol at 110112 (in vacuo). The anhydrous product had M.P. 196-197 (dec.). The infrared spectrum (KCl) now showed a strong band at 1755 cm.

Analysis.Calcd. for C H N O-HCl: Cl, 11.05; N, 8.72. Found: Cl, 11.01; N, 8.92.

EXAMPLE V A. 1- (4-phenyl-1-piperazyl) cycloheptene This enamine was prepared according to the procedure of Example IA using cycloheptanone as the cycloalkanone. The product was isolated in a yield of 27% M.P. 596l.

Analysis.--Calcd. For C H N N, 10.92. Found: N, 11.09.

B. 2-(4-phenyl-1-piperazyl)-10-oxobicyclo[3.4.1]

' decane Analysis.--Calcd. for C H N O: N, 8.97. Found: N, 9.21.

C. 2- (4p-henyl-1-piperazyl) -10-oxobicyclo [3.4.1 decane hydrobromide To the free base (6.0 g.) in methanol was added excess hydrogen bromide in 2-propanol. The salt was dissolved by the addition of just the required amount of water to the boiling alcohol suspension. The White crystals which formed amounted to 4.2 g., M.P. 226227.

Analysis.Calcd. for C H H O-HBr: Found: Br, 20.48.

EXAMPLE VI A. 2- (4-phenyl-1-piperazyl) -4-phenyl-9-ox0bicyclo [3.3.1]n0nane The free .base was prepared in benzene solution start ing with 1-(4-phenyl-1-piperazyl)cyclohexene and cinnamaldehyde. After removal of solvent the residue was stirred with Skelly A to give a solid. Recrystallization from benzene-Skelly A gave the bicyclic aminoketone in 36% yield, M.P. 167168;

vggf 1710 MIL-1 Analysls.Calcd. for C H N O: N (basic), 3.74. Found: N (basic), 3.72.

B. 2-(4-p'henyl-1-piperazyl) -4-phenyl-9-oxobicyclo [3.3 .1 ]nonane hydrochloride The salt was prepared in the usual manner from hydrogen chloride-isopropyl alcohol; M.P. 229230.

Analysis.--Calcd. for C H N O-HCl: Cl, Found: Cl, 8.48.

EXAMPLE VII 2-(4-m-CHLOR-OPHENYL-Q-OXOBICYCLO[3.3.1]NONANE A. 1 (4-m-chlorophenyl-1 -piperazyl cy clohexene This enamine was prepared according to the procedure of Example IA using 1-m-chlorophenylpiperazine as the piperazine derivative. The product was isolated in a yield of B.P. 170 (0.15 mm.).

Analysis.Calcd. for C H ClN N (basic), 5.06. Found: N (basic), 5.01.

B. 8a-(4-m-chlorophenyl-1-piperazyl) 4a,5,6,7,8,8ahexahydro-4H-1 -benzopyran This intermediate was prepared according to the procedure described for the previously mentioned aminopyrans using 1-(4-m-chlorophenyl-l-piperazyl)cyclohexene and acrolein. The material was isolated as an ivory colored solid in 85% yield, M.P. 88-92. Recrystallization from when stirred with cold methanol, yield 11.0 g., M.P.

AnalyszIa-Calcd. for C H ClN O: N (basic), 4.21. Found: N (basic), 4.26.

C. 2-(4-m-chlorophenyl) -9-0x0bicyclo[3.3.1]nbnane CIICla 1710 cm g) Analysis.Calcd. for c n cm oz N (basic), 4.21. Found: N (basic), 4.27.

D. 2-(4-m-chl0r0phenyl) -9-0x0bicycl0 [3.3.1]nnane hydrochloride The hydrochloride was prepared in HCl-i-PrOH from 6.17 g. of the free base (M.P. 9496); yield of salt, 6.25 g., M.P. 193 -l94 (dec.). Recrystallization from aqueous isopropyl alcohol gave 2.65 g. of analytically pure product, M.P. 195196 (dec.).

Analysis.Calcd. for C 'H ClN O-CHl: Cl, 9.59; N, 7.57. Found: Cl, 9.53; N, 7.48.

EXAMPLE VIII A solution of 52.0 g. (0.25 mole) of chalcone in benzene was added to a stirred solution of 60.5 g. (0.25 mole) of 1-(4-phenyl-l-piperazyl)-cyclohexene in benzene. After standing for 3 days, the benzene was removed in vacuo and the residual sirup was stirred with Skelly A. The solid material which formed was collected and washed with Skelly A, yield 48.5 g. (44%). M.P. 115- 117 11,25,9 1660 cm.- (medium) Two recrystallizations from benzene-Skelly A gave the analytical sample, M.P. 129.5-130.5.

Analysis.Calcd. for C H N O: C, 82.66; H, 7.56; N, 6.22. Found: C, 82.47; H, 7.34; N, 6.23.

B. 1-(4-phenyl-1-piperazyl) -2 (6) (I-phenyl-Z-benzoylethyl) -cycl0hexene In a 0.27 mole run carried out as described above the residual sirup obtained on concentration of the reaction solution was crystallized from methanol instead of Skelly A, yield 60%, M.P. 135136,

@013 1685, 1645 w. (mtmax.

10 in absolute ethanol and heated under reflux for 5 minutes. The crystalline product obtained (2.19 g.) had M.P. l32133; mixed M.P. with aminopyran from A was depressed 124126, mixed M.P. with enamine ketone from B not depressed.

EXAMPLE IX 2-phenyl-8a-(4-phenyl-1-piperazyl) -4a,5,6,7,8,8a-hexahydro-4H-1 -benz0pyr(m The reaction was carried out according to the procedure of Example VIII A using 0.05 mole quantities of acrylophenone and 1-(4-phenyl-1-piperazyl)cyclohexene. The yield of crude product was 75%, M.P. 87-91. Recrystallization from Skelly A-benzene and a further recrystallization from Skelly B gave the analytical sample, M.P. 96-97;

V319 1660 emf Analysis.Calcd. for C H N O: N, 7.49. Found: N, 7.40.

EXAMPLE X A. 1-(m-trifluoromethylphenyl) -4-(1-cyclohexenyl) piperazine This enamine was prepared according to the procedure of Example I A using l-m-trifiuoromethylphenylpiperazine as the piperazine derivative. The product was isolated in a yield 69%, B.P. l54169 (0.15 mm.).

Analysis.Calcd. for C H F N N (basic), 4.51. Found: N (basic), 4.53.

To a stirred solution of 46.5 g. (0.145 mole) of l-(mtrifluoromethylphenyl) 4-(l-cyclohexenyl)piperazine in 250 ml. of dry benzene was added 11.4 g. (0.20 mole) of acrolein in 25 ml. of dry benzene. The solution was stirred at 1015 for 30 minutes and then allowed to stand at room temperature 1 hour. After storing 12 hours in the refrigerator, the solvent was removed in vacuo and the residue dissolved in 500 ml. of dimethylformamide and 60 ml. of triethylamine. The solution was heated in a nitrogen atmosphere for 16 hours at 90. The solvent Was removed and the residue dissolved in ether. The solution was shaken with dilute hydrochloric acid. The aqueous layer was separated, made alkaline with sodium hydroxide solution, and extracted with chloroform. The extract was dried and concentrated in vacuo. Distillation of the residue gave 21 g. of material, B.P. 200-210 (0.25 mm.). Crystallization from Skelly B gave 6.5 g. of low melting solid.

Analysis.Calcd. for C H F N N (basic), 3.82. Found: N (basic), 3.84.

C. 2-(4-m-zriflu0r0methylphenyl-J-piperazyl) -9-0x0bicyclo- [3.3.1 ]n0nalze hydrochloride A solution of HCl in 2-propanol (1 mole-equiv.) was added to 6.0 g. of the free base. The salt was collected and dried, yield 4.0 g., M.P. 209-210".

Analysis.-Calcd. for C H F N -HCl: Cl, 8.80; N, 6.96. Found: Cl, 8.75; N, 7.00.

The various compounds described in the above examples are shown in Table I with their physical and chemical characteristics.

In summary this invention relates to a series of novel piperazyl substituted bicycloalkanones which have useful pharmacological activity to intermediate aminopyran derivatives prepared in the synthesis thereof and to openchain ketones prepared from such aminopyran derivatives.

What is claimed is:

1. A compound selected from the group consisting of compounds of the formula wherein R is a member selected from the group consisting of hydrogen and phenyl, R is a member selected from the group consisting of hydrogen and methyl, R is a member selected from the group consisting of hydrogen and chloro, R is a member selected from the group consisting of hydrogen and phenyl and X is a member selected from the group consisting of 26 8. A process for the preparation of a compound of the formula wherein R is a member selected from the group consisting of hydrogen and phenyl, R is a member selected from the group consisting of hydrogen and methyl, R is a member selected from the group consisting of hydrogen and chloro, R is a member selected from the group consisting of hydrogen and phenyl and X is a member selected from the group consisting of which comprises reacting a compound of the formula wherein R and X are as above defined, with a compound of the formula 0 R -c=0--t JR wherein R R and R are as above defined, to produce a compound of the formula gCT/ Q wherein R R R R and X are as above defined.

No references cited.

HENRY R. JILES, Primary Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,354,161 November 21, 1967 Robert Norman Schut It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 3, line 7, for N" read Et N column 4, line 69, for "lbenzopyran" read l-benzopyran column 8, line 13, for "C H H O" read C H N O line 34, for "C H N O" read C H N O line 65, for "when stirred with cold methanol, yield 11.0 g. read ether-iS opropyl alcohol gave purified product, column 9, line 30, for "CH1" read HCl column 10, line 35, after "yield" insert of line 50, for "60" read S0 column 5, line 3, for "activity" read activity,

Signed and sealed this 18th day of February 1969.

(SEAL) Attest:

Edward M. Fletcher, Jr. EDWARD J. BRENNER Attesting Officer Commissioner of Patents 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS OF THE FORMULA
 8. A PROCESS FOR THE PREAPARATION OF A COMPOUND OF THE FORMULA 